Abstract
It has been argued that some β-adrenoceptor antagonists may directly influence myofibrillar cross-bridge interaction in cardiac skinned fiber preparations of animal models. The present study investigates the effects of nebivolol, metoprolol and carvedilol on tension development of Triton X-100 skinned fibers obtained from human failing myocardium as well as on force of contraction and intracellular Ca 2+ transient in isolated trabeculae. In skinned fiber preparations, none of the β-adrenoceptor antagonists (10 μM) influenced Ca 2+ sensitivity of tension development or maximal Ca 2+ activated tension (DT max): control: EC 50 for Ca 2+: 1.28±0.05 μM, DT max: 14.09±0.59 mN/mm 2; nebivolol: 1.36±0.1 μM, 14.14±0.95 mN/mm 2; carvedilol: 1.32±0.11 μM, 13.83±0.90 mN/mm 2; metoprolol: 1.34±0.14 μM, 13.72±0.36 mN/mm 2. Simultaneous measurement of force and Ca 2+ transient in the presence of the β-adrenoceptor antagonists (3 μM) showed that the decrease in force of contraction was paralleled by a similar decrease in the intracellular Ca 2+ transient. In conclusion, none of the investigated β-adrenoceptor antagonists influenced Ca 2+ sensitivity of myofibrillar tension development in human failing myocardium.
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